Synthesis and in Vitro and in Vivo Evaluation of a Series of Dihydroisocoumarin Derivatives Conjugated with Fatty Acids, Alcohols, and Amines as Potential Anticancer Agents

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• 作者：Catherine A. Higgins ; Zoica Delbederi ; Kelly McGarel ; Timothy Mills ; Owen McGrath ; Stephanie Feutren-Burton ; William Watters ; Paul Armstrong ; Patrick G. Johnston ; David Waugh ; Hendrik van den Berg
• 刊名：Bioconjugate Chemistry
• 出版年：2009
• 出版时间：September 16, 2009
• 年：2009
• 卷：20
• 期：9
• 页码：1737-1751
• 全文大小：440K
• 年卷期：v.20,no.9(September 16, 2009)
• ISSN：1520-4812

文摘

In this paper, we report the synthesis and biological activity of a series of dihydroisocoumarin analogues conjugated with fatty acids, alcohols, or amines, of varying hydrocarbon chain length and degree of unsaturation, to the dihydroisocoumarins, kigelin and mellein, at the C-7 and C-8 positions on the core dihydroisocoumarin structure. These compounds were evaluated for their antiproliferative activity against human breast cancer (MCF-7 and MDA-MB-468) and melanoma cells (SK-MEL-28 and Malme-3M) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Two compounds conjugated with γ-linolenyl alcohol (18:3 n-6) demonstrated potent antiproliferative activity in vitro with one of these 4-hydroxy-3-oxo-1,3-dihydro-isobenzofuran-5-carboxylic acid octadeca-6,9,12-trienyl ester, demonstrating significant antitumor activity in vivo in a number of human tumor xenograft models.